Abstract 5143: Gene expression profiles associated with induction treatment response in pediatric patients with acute lymphoblastic leukemia type B
Authors: Yulieth X. Torres-Llanos, Jovanny Zabaleta, Nataly Cruz-Rodriguez, Sandra M. Quijano, Paula C. Guzmán, Iliana De Los Reyes, Ana M. Infante, Liliana Lopez, Alba L. Combita
Journal: Cancer Research (2022)

Abstract Acute lymphoblastic leukemias (ALL) are the most common hematopoietic neoplasms in children. Survival in developed countries is &amp;gt;80%, while in Colombia is ≤60%. These differences have been related to different factors, including genetic and epigenetic alterations, which could regulate chemoresistance mechanisms. Currently, some genetic alterations have been used to classify patients in a risk group, but a genetic profile that can be applicable to most patients to predict with high sensitivity the response to induction chemotherapy, improve the risk classification and predict survival is highly needed. We aim to identify gene profiles associated with response to induction chemotherapy in pediatric patients with ALL-B. Methods: Bone marrow samples were collected from 27 patients with a new diagnosis of B-ALL. Blasts were separated and purified according to the expression of the CD19 and CD34. RNA was extracted and used as template for genomic libraries. RNA-seq was done using the Illumina platform, and the reads were aligned and quantified using Partek Flow. DEseq2 was used for statistical analysis and to determine the differentially expressed genes (DEG) between the patient groups. Response to induction treatment was defined (flow cytometry) as positive or negative minimal residual disease (MRD) as percentage of residual blasts &amp;gt;0.01% or &amp;lt;0.01%, respectively. Three comparison groups were defined: 1) true responders (MRD- at day 15 and MRD- at the end of induction) vs. true non-responders (MRD+ at day 15, and MRD + at the end of induction), 2) MRD- vs MRD+ at the 15 day of induction; 3) MRD- vs MRD+ at the end of induction. Genes with a p &amp;lt;0.05 and a fold change &amp;gt;2 were chosen. Additionally, an enrichment analysis was performed to determine the signaling pathways associated with treatment response. Results: 159 DEGs were found among MRD- vs MRD+ at day 15 of the induction, 200 DEGs were identified between MRD- vs. MRD+ at the end of induction, and 153 DEGs were found between patients classified as true responders vs. true non-responders. Additionally, to determine the genes that could be predicting the response to treatment, a comparison was made between the DEGs of each group of patients analyzed, finding 50 genes in common. Interestingly, the genes identified are associated with differentiation of stem cells (HOXB2), metabolic process (ST8SIA6, SPHK1, HPGD), immune response (CFH, PAR2, NFAM), cell-cell signaling (PEAR1, PTGIR), and ion transmembrane transport (SLC2A7, SLC45A3). The overexpression of these genes is associated with a poor response to induction chemotherapy. Conclusion: We identified 50 genes associated with the response to induction chemotherapy in pediatric patients with ALL-B. Those genes are associated with signaling pathways that could be explaining the lack of response in patients and might serve as possible biomarkers of response to induction treatment. Citation Format: Yulieth X. Torres-Llanos, Jovanny Zabaleta, Nataly Cruz-Rodriguez, Sandra M. Quijano, Paula C. Guzmán, Iliana De Los Reyes, Ana M. Infante, Liliana Lopez, Alba L. Combita. Gene expression profiles associated with induction treatment response in pediatric patients with acute lymphoblastic leukemia type B [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5143.